Azepines and Piperidines with Dual Norepinephrine Dopamine Uptake Inhibition and Antidepressant Activity
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- 作者：Dean G. Brown ; Peter R. Bernstein ; Ye Wu ; Rebecca A. Urbanek ; Christopher W. Becker ; Scott R. Throner ; Bruce T. Dembofsky ; Gary B. Steelman ; Lois A. Lazor ; Clay W. Scott ; Michael W. Wood ; Steven S. Wesolowski ; David A. Nugiel ; Stephanie Koch ; Jian Yu ; Donald E. Pivonka ; Shuang Li ; Carol Thompson ; Anna Zacco ; Charles S. Elmore ; Patricia Schroeder ; JianWei Liu ; Christopher A. Hurley ; Stuart Ward ; Hazel J. Hunt ; Karen Williams ; Joseph McLaughlin ; Valerie Hoesch ; Simon Sydserff ; Donna Maier ; David Aharony
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：January 10, 2013
- 年：2013
- 卷：4
- 期：1
- 页码：46-51
- 全文大小：311K
- 年卷期：v.4,no.1(January 10, 2013)
- ISSN：1948-5875
文摘
Herein, we describe the discovery of inhibitors of norepinephrine (NET) and dopamine (DAT) transporters with reduced activity relative to serotonin transporters (SERT). Two compounds, 8b and 21a, along with nomifensine were tested in a rodent receptor occupancy study and demonstrated dose-dependent displacement of radiolabeled NET and DAT ligands. These compounds were efficacious in a rat forced swim assay (model of depression) and also had activity in rat spontaneous locomotion assay.